The present invention relates to a dialyzer used in dialysis. More specifically, it relates to an internal filtration accelerating-type dialyzer which can increase an internal filtration rate and an internal backfiltration rate within the dialyzer.
For therapy of patients whose renal function is impaired, for example, patients whose function of removing waste products or the like in blood is impaired because of renal insufficiency or the like, therapy by blood purification such as hemodialysis or hemodialytic filtration has so far been performed. In this blood purification therapy, urea, creatinine, uric acid, low-molecular proteins, water and the like accumulated in blood are removed by bringing the blood into contact with a dialyzate through semipermeable membranes in a dialyzer.
In recent years, a substance that causes amyloidosis, which is one of complications in dialysis, has been identified as β2 microglobulin having a molecular weight of 11,800 (F. Gejyo et al., Kidney International, vol.30, pp. 385–390, 1986). Since β2 microglobulin having a high molecular weight has a low diffusion rate, removal efficiency is higher by hemofiltration than by hemodialysis. Further, since a substance having a low molecular weight, such as urea, has a high diffusion rate, removal efficiency is higher by hemodialysis than by hemofiltration. Accordingly, a hemodialytic filtration therapy (HDF) being a combination of hemodialysis and hemofiltration has been conceived. In the HDF therapy, filtration of a large amount of fluid is conducted with a dialyzer and a replenisher is supplied in a blood circuit. Therefore, an exclusive device with a complicated structure is required.
Meanwhile, a dialyzer excellent in product permeability and water permeability, which can remove β2 microglobulin having a high molecular weight, has been developed. It has been found that such a dialyzer excellent in product permeability and water permeability allows filtration and backfiltration between a blood and a dialyzate via a semipermeable membrane (hereinafter referred to as internal filtration and internal backfiltration) even when forced filtration by dewatering is not performed (M. Schmidt et al., Blood Purification 2: 108–114,1984). Accordingly, a hemodialytic filtration method that performs filtration and replenishment by increasing an amount of internal filtration and an amount of internal backfiltration has been proposed. Additionally, an internal filtration accelerating-type dialyzer capable of increasing dialysis efficiency, which is used in the hemodialytic filtration method, is being developed.
Usually, the internal filtration and the internal backfiltration do not occur at a same position within a dialyzer. Since blood and a dialyzate are passed through a dialyzer in directions opposite to each other, a fluid having a higher pressure moves to a fluid having a lower pressure via a semipermeable membrane regarding the blood and the dialyzate. That is, there is a tendency that the internal filtration occurs on a blood inflow side within a dialyzer and the internal backfiltration occurs on a blood outflow side within a dialyzer.
For increasing an internal filtration rate and an internal backfiltration rate in a dialyzer, it is necessary to increase a pressure loss along a blood flow path or a dialyzate flow path. The pressure loss along the flow path is represented by the Hagen-Posuille formula which is a pressure loss inducing formula of laminar flow in a cylindrical tube.ΔP=8 μLQ/πR4                (ΔP: pressure loss of a flow path [Pa],        μ: viscosity of a fluid [Pa·s],        L: length of a flow path [m],        R: radius of a flow path [m],        Q: volume flow rate [m3/s])        
It is found that to increase the pressure loss ΔP along the flow path, the volume flow rate Q may be increased, the sectional area of the flow path πR2 may be decreased or the length L of the flow path may be increased.
For increasing an internal filtration rate and an internal backfiltration rate of a dialyzer, a dialyzer, the length of the flow path of which is increased by increasing a total length, (Japanese Patent No. 2961481) and a dialyzer, a sectional area of a blood flow path of which is decreased by decreasing an inner diameter of a hollow fiber membrane, (F. Dellanna et al., Nephrol Dial Transplant 11, Suppl. 2: 83–86, 1996) have so far been known.
However, in the dialyzer with the total length increased, for obtaining effects of sufficient acceleration of internal filtration and internal backfiltration, the length of the flow path has to be increased to more than twice the length of the flow path in an ordinary dialyzer. Such a dialyzer is impractical. Further, in the dialyzer with the inner diameter of the hollow fiber membrane decreased, there is a likelihood that irregularity occurs in the inner diameter of the hollow fiber membrane during manufacture or blood remaining in lumens of the hollow fiber membranes after use of the dialyzer is increased.
Further, there has been proposed as a dialyzer, a cross-sectional area of a dialyzate flow path of which is decreased by increasing a packing ratio of hollow fiber membranes, a dialyzer, a hollow fiber bundle of which is shrunk with a net or the like (Japanese Patent Laid-Open No. 168525/1996 and Domestic Republication WO 98/22161). However, in the dialyzer with the hollow fiber bundle shrunk, the diameter of the hollow fiber bundle has to be decreased more than necessary for inserting the hollow fiber bundle into a case. Therefore, the hollow fiber membranes might be ruptured and the packing ratio of the hollow fiber membranes inserted into the case is not high enough.
Moreover, as a dialyzer with a decreased sectional area of a dialyzate flow path, a dialyzer in which a bonded mat having a property of being swelled with a dialyzate is introduced in a dialyzate, flow path (Japanese Patent Laid-Open Nos. 192031/1996 and 9684/1999, Domestic Republication WO 98/22161), a dialyzer in which a bag-shaped member is introduced into a dialyzate flow path and the bag-shaped member is swelled by introducing therein a physiological saline or the like at the time of using the dialyzer (Japanese Patent Laid-Open Nos. 394/1999 and 319080/1999, Domestic Republication WO 98/22161), a dialyzer in which a sectional area of a dialyzate flow path is capable of changing by changing the case of the dialyzer with pressure applied from outside the case (Japanese Patent Laid-Open No. 319079/1999) and the like have also been developed.
In a dialyzer in which a bonded mat having a property of being swelled with a dialyzate is introduced, the bonded mat has itself a thickness so that an amount of the product that can be introduced into the dialyzer is limited. When the amount of the bonded mat is large, it is difficult to insert the hollow fiber bundle into the case of the dialyzer. Meanwhile, when the amount of the bonded mat is small, the sectional area of the dialyzate flow path is not sufficiently lowered. Further, in a dialyzer with the bonded mat having the swelling property introduced being wound, the hollow fiber bundle is previously inserted into the lumen of the product having a far smaller inner diameter than the inner diameter of the case and then inserted into the case so that the hollow fiber membranes might be ruptured.
On the other hand, in a dialyzer in which a bag-shaped member is swelled, the structure is complicated and a force exerted in swelling the bag-shaped member is also exerted on the case of the dialyzer. Thus, improvement in the case material is required for the case to have a satisfactory rigidity. Further, in a dialyzer, the sectional area of the dialyzate flow path of which is capable of changing by changing the case thereof, a part of the case is changed by pressure applied from outside of the case. With such a dialyzer, pressure has to be continued to be applied during changing of the sectional area of the dialyzate flow path so that the structure of the dialyzer is more complicated.